This invention relates generally to magnetic resonance spectroscopy (MRS), and more particularly the invention relates to rapid chemical shift imaging of metabolically active substances.
Nuclear magnetic resonance (NMR) has been applied to spectroscopy as an analytical technique in obtaining information about molecular structure, dynamics, and molecular interactions. However, until recently the application of MRS in vivo has been limited by low sensitivity due to low magnetic energy of nuclear spins compared with thermal energy at room temperature.
Recently, hyperpolarization techniques have greatly increased the detection sensitivity of nuclear spins other than protons which enables fast imaging of these nuclei. Their molecular distribution in vivo can be visualized in a clinically relevant time window. See Golman et al., Molecular Imaging Using Hyperpolarized 13C, The British Journal of Radiology, Special Issue, 2003.
With signal-to-noise ratio (SNR) enhancements on the order of the 100,000-fold, dynamic nuclear polarization of metabolically active substrates (e.g., 13C-labeled pyruvate or acetate) theoretically permits in vivo imaging of not only the injected agent, but also downstream metabolic products. This feature of hyperpolarized MR spectroscopy provides a unique chance to non-invasively monitor critical dynamic metabolic processes in vivo under both normal and pathologic conditions. Important applications include tumor diagnosis and treatment monitoring as well as assessment of cardiac function.
When using hyperpolarized samples, the magnetization decays towards its thermal equilibrium value and the enhanced signal is not recoverable. Therefore, fast acquisition schemes are important. Furthermore, due to very low natural abundance of 13C combined with its low degree of polarization at thermal equilibrium, virtually no background signal is present. Depending on the substrate, this can produce relatively sparse spectra as is the case for a bolus injection of hyperpolarized [1-13C] pyruvate where the metabolic products detectable by 13C-MRS comprise lactate, alanine, and bicarbonate. While a number of fast spectroscopic imaging methods have been proposed for more general in vivo MRS applications, the need for high speed in data acquisition combined with the limited spectral content restrict known spectroscopic imaging methods for hyperpolarized agents.